The UK NHS – 70 years but why was it necessary?

The UK NHS at 70 years  – but why was it necessary?


The UK is celebrating the introduction of the National Health Service, 70 years ago. It is however a time for reflection rather than celebration. The "celebrations" usually describe advances in medical practice that have occurred in many nations, advances that are far from specific to the UK NHS.

Why is it that in 1948 the UK introduced a nationalised health care system (known as the NHS) whereas this had not happened in other countries and has not happened subsequently outside the UK?

The NHS was not introduced out of ideology but out of necessity. The many independent hospitals were effectively bankrupt, and rescue by central government was the only acceptable option at the time. It proved to be very successful.

Blackburn Royal Infirmary, opened 1862

The voluntary hospitals of the UK, the infirmaries, had developed widely during the 19th century in response to an increasing number of industrial accidents. They were primarily centres of surgery, but staffed mainly by physicians; surgeons had a technical function without day-to-day patient care. 

The local authorities, the town councils, also developed hospitals, but they were more orientated to chronic diseases, and also tuberculosis, acute fevers, care of children, and maternity care. There was generally rivalry rather than co-ordination between the hospitals and the infirmaries.


The local authority hospitals were funded by the town council, but there was no formal or regular funding of the infirmaries. They had been set up by large donations from local industrialists, and funding continued to be on the basis of philanthropy. Donations from citizens were constantly required.

Bismark

During the late 19th century hospital activity was increasing substantially but philanthropy was diminishing. The infirmaries were drawing on their financial reserves. A new and regular source of funding was necessary and the answer lay in Germany, administered by Chancellor Otto von Bismark.

Bismark had introduced social insurance, an insurance system in which each week working people paid  a compulsory income-related tax into a fund, so that at times of need (illness, unemployment, major injury, old age) they would receive payment from the fund. This was an important social advance, very relevant to the new industrial nations.

Lloyd George

Social insurance was introduced in the UK in 1911, by the Liberal party Chancellor of the Exchequer David Lloyd George. It included general practice family medicine, but not hospital care. This had long-term ramifications that we experience in the 21st century.

General practice family medicine adapted well to social insurance, but the doctors were paid on the basis of an annual capitation fee, rather than payment by item of service which had developed in other European countries. 

The infirmaries were desperate for the introduction of social insurance. It would mean that, as in the German model, an episode of  hospital care would generate a bill, which would be passed from the patient to the insurance organisation that collected the social insurance fund. The vital part of the process was that an increase  activity would generate increasing income to the infirmary.

This is the model that proved to be very successful in other European countries. It was not introduced in the USA due to failure to pass legislation for a health tax that would be compulsory – the Statue of Liberty represents liberty from government laws.

But  in the UK hospital funding from the 1911 Social Insurance was not to be. The proposal proved to be unacceptable to the hospital consultant body of the British Medical Association (BMA). The consultants felt that a cash payment from patient to doctor was right and proper, and they appear to have given no consideration to the plight of the infirmaries.

Clement Attlee

And so the infirmaries continued after World Ward One with serious underfunding that was not sustainable. The crisis of the 1930s was postponed by the greater challenge of World War Two. However within government, rescue of the nation's infirmaries (including the major teaching hospitals) was being planned. The proposals were accepted by the new Labour government in 1945 (Prime Minister Clement Attlee) and the NHS was introduced on July 5th 1948. The key politician was the charismatic Welsh Minister of Health, Aneurin Bevan.

Aneurin Bevan

The option of local government taking over the infirmaries was against the wishes of the BMA and it would not have helped as a nation funding system was essential, along the lines of the German Social Insurance. But in the UK there was no insurance organisation that could deliver the enormous task ahead. A solution was urgent. The government stepped in to fund hospital and indeed all health care from central taxation. The expenditure of hospitals in 1947 was  provided as income for the hospitals in 1948 and beyond.

The opportunity was taken to integrate all hospitals within a community under a Hospital Management Board. Hospital care was free at the point of access.

The immediate crisis was solved, but activity increased at a greater rate, no doubt because it was now free to all, and this continued continually during the subsequent 70 years. The financial pressures were effectively transferred to central government, which had taken responsibility for funding health care through the new NHS.

If an insurance system of funding had been adopted, hospital income would have increased with activity. However funding as a block grant by central government has meant that activity and staffing (70% of expenditure) have been constrained to keep within the cash allocation.

The tension has continued for 70 years. We end up with the UK NHS being very cost-effective (one measure of efficiency) with a large activity being delivered within a certain defined budget. On the other hand other European countries have higher expenditure, more hospital beds, more doctors and other staff than the UK. They also generally have better overall health outcome measures.

The NHS seems to be inadequately funded, but there is also a serious recruitment problem, of doctors and nurses in particular. This restricts the opportunities of spending any additional funding.

Will the UK NHS change to having an insurance base? The answer is "No". Although as in 1911 it would be popular with health care providers, it would be an enormous change and it would be strongly resisted by government and the Treasury in particular. 

The NHS is extremely popular with the public. No doubt it will continue despite its faults and permanent underfunding.

High cholesterol is good

We generally hope for long life, and this has been increasingly the pattern during the past twenty years or more. Public health is active to help us achieve a long life and it is expected that young people today can look forward to 90 years of life. This is very different from 100 years ago. My father's eldest brother James Grimes was born in 1900, when all seemed to be well with increasing prosperity. But it was not to be for James. He was killed on June 8th 1918, in the Battle of Albert (HQ of the British Army of the Somme). The memories of James and countless other young men killed a century ago live on in the carefully-tended war cemeteries in northern France. 

How life and its expectations can so quickly come to an end.  

Today we are fortunate in worrying about cholesterol rather than war.

High cholesterol is good

It is remarkable that people are still told that cholesterol is bad. Many people go for a routine annual visit to their primary care physician and the nurse will take blood for cholesterol. If it is judged to be high, and this will be the case in 85% of people by arbitrary and questionable definition, then the individual will be advised to take a low fat diet and might be started on a statin medication.

We know from previous Posts that a high blood cholesterol is a disadvantage only in men below the age of 50. In men and women above the age of 60, high cholesterol appears to give a survival advantage.

New information supports this. A study from Israel has recently been published and it clearly shows that survival is better when blood levels of cholesterol are higher.

In this study, the 305 subjects had heart failure, and in 74% the underlying disease process was coronary heart disease (CHD). The average age was 70 years. The average follow-up was 11 years, but the time sequence on the graphs was up to 20 years, the maximum follow-up time. The subjects were recruited over a period of several years rather than them all being recruited and the same time. The graphs are called "Cox regression curves", the standard way to present survival when recruitment varies over time. 

The subjects were initially divided into two groups, less than 70 years of age (122) or greater than 70 years of age (183), and then further subdivided based on blood levels of cholesterol. The measure chosen was LDL-cholesterol. This has no mathematical relationship to total cholesterol, but is usually about half.

The two groups were less or more than 100 mg/ml, which equates to 2.8 mmol/L, the measure in use in Europe.

Figure 1 shows the survival of all subjects based on cholesterol levels.

Figure 1. Survival of all ages 

It is clear that long-term survival is greater (blue curve) in those with the higher levels of LDL-cholesterol.

Figure 2 shows the survival of subjects aged 70 years or less, again based on levels of LDL-cholesterol.

Figure 2. Survival of those 70 years of age and younger 

The survival advantage of a high cholesterol (blue line) is similar in this younger age range.

Figure 3 shows the survival of subjects aged greater than 70 years, again based on levels of LDL-cholesterol.

Figure 3. Survival of those older than 70 years.

In this older age group the survival lines are much reduced, as would be expected. The survival lines run closer together and the advantage of a high cholesterol is not as great.

This study adds weight to previous observations that dogma that a high level of cholesterol in the blood is dangerous is wrong. The diet-cholesterol-heart hypothesis should be abandoned. 

Routine testing of blood level of cholesterol is pointless.

Causes of death in 2017 – the decline of coronary heart disease

To determine the causes of death of the population is not easy. The data from the UK Office of National Statistics (ONS) are comprehensive, complicated, and inevitably a few years after the event. An alternative is look out for samples, the causes of death of smaller groups rather than the population as a whole. This inevitably produces biases: if the sample is not random (a complex process) it might not be fully representative of the population. However it should give some idea of why people die.

There is an opportunity in a study of doctors. Doctors might not be entirely representative of society but the seminal study of the dangers of cigarette smoking, conducted by Sir Richard Doll in the 1950s, was a study of doctors. Its message was applied to the population as a whole.

Doctors are thought to have a longer than average life expectancy. This goes with affluence and a high level of education, both of which are related to longer life expectancy. There is a quoted study of doctors that states that underlying the longer life expectancy, the ways in which they differ from the general population include: only rarely visiting a doctor, taking very few medications, avoiding screening tests, and drinking rather a lot of alcohol. To this must be added in recent decades, that very few smoke cigarettes. However this alleged study is rather cynical and might be apocryphal. 

At present, average life expectancy in the UK is 79.4 years for males and 83.1 for females, overall 81.6. So let us look at doctors.

Obituaries

In the British Medical Journal each week we can usually find about six obituaries. In recent years most of these have given the cause of death in addition to personal and career details. So here we have up-to-date causes of death with age and sex, and this is an important source of information.

I have recorded these obituaries during 2016 and 2017. 

I have been particularly concerned to determine the current causes of death. We are still told that coronary heart disease (CHD) is the most important cause of death, but I have doubted this now that the epidemic has come to an end. What proportion of deaths are due to coronary heart disease at the present time?

I have recorded and analysed 568 consecutive obituaries. All give date of birth and death so that age of death profiles can be identified. 415 of these gave the cause of death. 

There are obituaries for 450 male doctors and 118 for females. This difference is inevitable as half of the total were born before the year 1930, a time when very few women entered medical training.

The overall age of death profile is as follows:

Figure 1. Age profile of deaths of doctors, 2016-17

Figure 1 shows the age at death (vertical axis) for each of the 568 individuals. Each vertical column on the horizontal axis represents one doctor, the height of the line indicating age at death. It allows us to see that the 50% median age at death is 87 years. It also shows the few early deaths (on the right).

Analysis of deaths

The causes of death, when given, must be grouped. This can be difficult as the important features are organ and disease type. For example "brain tumour" can be grouped under "brain" or "cancer". Similarly, "pneumonia" can be grouped under "lung" or "infection". I think that understanding is better if cancers are grouped together, and infections are grouped together. Otherwise the organ is the best grouping. I hope this is clear in the figures below.

No deaths are identified as being due to suicide, and the confidentiality of a suicide death is understandable. The two youngest men to die were age 34 and 35 years The cause of their deaths are not given and they might have taken their own lives.

For the purpose of analysis it is more informative to separate male deaths from female deaths.

Deaths of male doctors.

Of the 450 obituaries of male doctors, the cause of death is given in 316.

The average age at death of the 450 is 84 years, compared to 79.4 years for the current national average for men.


The median age at death of male doctors is 87 years, meaning that half died after that age.

Only 4 male doctors (0.9%) died before the age of 50 years. 2 of these died in cycling accidents. The cause of death in the other two is not given (as mentioned above, possibly suicide).

Only 37 (8.2%) died before the age of 65 years. 

Deaths of female doctors.

Of the 118 obituaries for female doctors, 89 give the cause of death.

The average (mean) age at death of the 118 is 77 years. The median age at death of females is 83 years, meaning that half of the deaths occurred after this age.

The average age at death is surprisingly early, the national average for females being 83 years. It reflects a number of early deaths of female doctors, many more than male deaths. This does not appear to be representative of society and was probably an unfortunate and atypical cluster of early deaths.

9 female deaths (7.6%) occurred below the age of 50 years. Of these 5 were due to cancer (not breast), one from brain haemorrhage (age 45) and one following aortic arch replacement (age 31), extremely hazardous cardio-vascular surgery. Another very young female died at the age of 33 due to brain tumour, and another aged 35 due to malignant sarcoma.

32 of the deaths (27.1%) occurred before the age of 65 years compared to 8.2% in males. There were 5 deaths from breast cancer between the ages of 50 and 65. 

Further details of deaths of male and female doctors are shown below.

Details - male deaths


This is the analysis of 316 recorded causes of death in male doctors.

Figure 2. Deaths of male doctors

34% of all recorded male deaths are from cancer (Figure 3). The second major category is diseases of the brain and nervous system, 18.3%.  Heart disease was responsible for only 10% of deaths, the same as old age.

Figure 3. Fatal cancers in male doctors
(percentage is of total deaths)

The most frequent fatal male cancer is cancer of the prostate, but it is the cause of death in only 6% of deaths in which the cause is given. Colon cancer and brain tumour are in second and third position. 11 of the cancer deaths did not name the cancer site.

The second major category is Brain and Nervous System , and the details can be seen in Figure 4.

Figure 4. Death from diseases of the brain and nervous system in male doctors
(percentage is of total deaths)

Dementia is the major cause of neurological death. The cause of dementia is not specified in 9 of the 22 deaths. Alzheimer's disease is specified in 7, vascular dementia in 4, and Pick's disease in 2. Death from motor neurone disease is not as rare as might be thought, 5 deaths, the same as brain haemorrhage.

We have always been told that heart attacks (myocardial infarction, MI) and coronary heart disease are responsible for more than 25% of male deaths. However this is far from true in doctors in the early 21st century century.

Figure 5. Death from diseases of the heart in male doctors 
(percentage is of total deaths)

Of the 316 recorded deaths, 34 (10.7%) are the result of heart disease. Heart failure is the most common within this group. Myocardial infarction and coronary heart disease were responsible for only 11 deaths, 3.5% of the total. 

The ages of the 11 male doctors who died from myocardial infarction and coronary heart disease are 52, 72, 72, 82, 86, 88, 88, 90, 90, 92, 94 (mean 82, median 87). Most are therefore very elderly and only one died from myocardial infarction before normal retirement age.

This is confirmation of my previous Blog Posts that the epidemic of coronary heart disease is now at an end.

There are 5 sudden deaths with the precise cause not recorded. It is likely that some of these would be the result of myocardial infarction, but it would make little difference to the remarkably low number of coronary heart disease deaths. Suicide could be be included under sudden death.

Death from trauma is not common but it is perhaps disturbing that 3 deaths were from cycling accidents. The ages of these individuals were 37, 43, and 60 years. The ski-ing death was at the age of 66 years.

Figure 6. Death from trauma in male doctors 
(total deaths 316)

Old age is now an important cause of death, in this study between the ages of 86 and 106 years.

Figure 7. Death from old age in male doctors 
(percentage is of total deaths)

More than 10% of men dying as the result of old age can be seen as a triumph. It might be the ambition of us all to die from old age rather than a specific disease, but the down-side is that death from old age is a slow process. 

The main lung disease causing death is pulmonary fibrosis (7 out of 16). The main infection causing death is pneumonia (20 out of 25).

Details - female deaths

The analysis is of 89 female doctors in which the cause of death is specified.

Figure 9. Deaths of female doctors

As with men (34.1%) cancers are the most common causes of death in women (47.2%).

The cancers causing female deaths are as follows.

Figure 10. Fatal cancers in female doctors
(percentage is of total deaths)

The most common cancer is breast cancer (10.1% of all female deaths). Cancer of the pancreas was responsible for 6.7% of deaths, higher than in men (2.5%). Death from brain tumours is the same in both males (3.2%) and females (3.4%).

The disease of the brain and nervous system most commonly causing death is dementia (including Alzheimer's disease), causing 7.8% of female deaths (6.9% in males).

Figure 11. Fatal diseases of brain and nervous system in female doctors
(percentage is of total deaths)

Death from stroke is less common in women (3.4%) than in men (6.3%). Death from motor neurone disease is again uncommon but significant.

Only 3 females died from heart disease, 1 from heart failure (aged 93 years) and 1 each from myocardial infarction and coronary heart disease. Just 3.4 % of female deaths from heart disease is very low,  lower than in males (10.7%) as expected. The ages of the two females who died from myocardial infarction and coronary heart disease are quite young at 51 and 70.

Deaths from infections are 6 from pneumonia and 1 from meningitis.

Deaths from trauma include 2 road traffic accidents (age 56 and 93), 1 fall (age 90), and 1 ski-ing accident (age 58).

Figure 12. Death from old age in female doctors
(percentage is of total deaths)

As with males (10.7%), old age is now a major cause of death in females, 10.1% (age range 78 to 103).

Old age

Perhaps deaths from "old age" are even greater, in both male and female doctors. Let us look at deaths from "pneumonia" in both males and females, shown in Figure 13.

Figure 13. Deaths from pneumonia, showing age at death.

We can see the ages at which the deaths occurred. Of the 22 deaths, 17 died at the age of 90 or beyond. Were these deaths in reality due to old age, with "pneumonia" simply accompanying the inevitable? If we ascribe the pneumonia deaths to old age, then the total deaths from old age become 16.5% for male and 14.6% for females doctors.

Conclusions


This is an up-to-date view of how people in the UK die, now. The example is doctors, not completely representative of the population. Although the age at death might be greater than average, there is no reason to expect that the causes of death are not representative.

It would have been interesting to repeat the present study of doctors comparing with obituaries in the British Medical Journal in previous decades. This has not been possible because it is only in recent years that causes of death have been given.

We have seen that cancers are now the main cause of death, of both males (about one third) and females (about one half). During the latter half of the 20th century the major cause would have been coronary heart disease. The pattern of cancers is not surprising – breast in female and prostate in males. In this study death from colon cancer is much more common in males than in females. 

The rapid decline of deaths from coronary heart disease is responsible for cancers taking first place. This is clear from the overall greater life expectancy. If there were an absolute increase in cancer deaths overtaking coronary heart disease deaths, then we would see people dying younger.

The second major category of death is diseases of the brain and nervous system, in both sexes. Dementia is the major category of fatal brain disease. 

Heart disease is the third group of causes of death of male doctors. Heart failure is most common in this group, more common than coronary heart disease, which accounts for only 3.5% of all deaths in males.

Old age is the fourth category in males and the third category in females, more than 10% in both. In males death from old age is three times more likely than death from coronary heart disease, and in females five times more likely. This is remarkable.

It is interesting that "old age" is now an accepted cause of death. In fact a major purpose of medicine is to enable people to die from old age, to "conk out" at some time around 90 to 100 years of age. Another purpose of medicine should be to enable this to be a peaceful rather than a medicalised process. Coroners in the UK have been reluctant to accept "old age" as the cause of death, but this is obviously changing.

Infections are also high in the cause of death in males and females, pneumonia being the most common fatal infection. These are potentially preventable causes of death.

It is sad to see premature deaths from trauma, 3 fatal cycling accidents and 2 fatal ski-ing accidents in particular.

The main message from this study is the major decline from death from coronary heart disease, which is no longer a major cause of death. 

11 male doctors died as a result of myocardial infarction or coronary heart disease, just 3.5%. Death from old age is three times more likely.

Only 2 females out of 89 died from myocardial infarction or coronary heart disease  This is only 2.25%, and means that death from old age is now five times more likely. 

The 20th century pandemic of coronary heart disease is now clearly at an end.

Statins are Antibiotics

The anti-bacterial effect of statins

In 2006 I suggested in an article in The Lancet that in addition to their ability to reduce blood levels of cholesterol, statins had effects similar those of the sun and vitamin D. They have a variety of actions that can improve health, among them to improve outcome from infection. These have been empirical observations but we can now see something of the mechanisms involved. 

The sun is alleged to be the best disinfectant, and we know that vitamin D amplifies the protective inflammatory response to infection. But what about statins? It now appears that statins do not obviously enhance immunity, but they have a direct anti-bacterial action.

Read on.

On the UK television recently I watched a travel programme in which the presenter, Joanna Lumley, visited a fisherman called Sergei in his family home in Irkutsk ("Big Cat Village"), adjacent to Lake Baikal in Siberia. In the kitchen there was a large bottle that contained a liquid in which there was a mould or fungus, known as "Manchurian Mushroom". The bottle of liquid was called "Kombucha" and Sergei explained that this was the traditional family medicine, to be taken at times of illness.

Kombucha

It would appear that moulds have been used for several centuries for health benefits and in particular to treat skin infections. In his excellent book The Diet Myth, Tim Spector suggests that of all foods that are alleged to be good for us, mouldy cheese is the main one that stands up to scrutiny. 

However the important step forward was the accidental discovery by Sir Alexander Fleming in 1928 that the mould Penicillium notatum was able to produce a powerful anti-bacterial compound. It inhibited the growth of the important human pathogen Staphylococcus aureus, which he was investigating at the time. The active compound produced by the mould became known as penicillin. 

Other moulds were subsequently investigated for antibiotic properties, with streptomycin being isolated in 1943 from the soil fungus Streptomycin griseus. The first of the antibiotic group cephalosporins was produced from a mould discovered in 1945 in a sewage outlet in Sardinia. 

It was realised that the value of antibiotics lay in the inhibition of bacterial metabolic pathways and one that had been identified as fundamental was the 3-hydroxy-3-methylglutaryl-Coenzyme A  (HMG-CoA) pathway. This pathway synthesises the very important cholesterol, and it was thought that blocking this pathway would seriously damage micro-organisms.

In 1971 the microbiologist Professor Akira Endo in Japan discovered a natural inhibitor of the pathway in a broth of the mould of Penicillium citrinum. The compound, which was named compactin or mevastatin, inhibited the enzyme HMG-CoA reductase. The first statin had been identified.

Professor Akira Endo

A more powerful HMG-CoA reductase inhibitor was identified in the fermentation of Aspergillus terreus, in the laboratories of Merck pharmaceuticals. It was called mevinolin, or lovastatin. The group of compounds isolated became known as statins, and the anticipated role was as to kill bacteria.

The antibacterial action turned out to be weak, but the inhibition of cholesterol synthesis and the ability to reduce blood level of cholesterol was powerful. Thus began the highly successful development of statin cholesterol-lowering medications. Statins came to be taken daily by many rather than infrequently by few.

Antibiotic resistance

There is at present great concern about widespread resistance of many pathogenic bacteria to antibiotics in current use. The challenge is a future without effective antibiotics.

In recent years there has been a failure of pharmaceutical companies to develop a new antibiotics, and there is not the slightest reason to expect a government body to be any more successful. The problem is that the cost of developing any novel pharmaceutical agent is almost $2 billion. The recovery of this investment is challenging. There is a view that a new antibiotic must be held in reserve for use only when absolutely necessary. An antibiotic is given for only a short course of a few days, and so the cost per tablet will inevitably be very high, and perhaps prohibitively so. The appearance of a novel antibiotic is by no means certain, and the chance of recovering development costs is very doubtful, especially if its use is restrained.

But the cost of development would be much reduced if an existing medication, fully tested with a good safety profile in the short term, could be shown to be antibacterial. And so now there is a renewed interest in statins, to be used as originally designed.

The anti-bacterial effect of statins in vitro

Statins exhibit antibacterial activity against a wide spectrum of Gram-positive bacteria. These include the following: 

• Staphylococcus epidermidis, Streptococcus anginosus;
• Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus salivarius, Streptococcus sanguinis  (these bacteria are found typically in the mouth);
• Enterococcus faecalis, Enterococcus faecium, Lactobacillus casei (these are intestinal bacteria);
• Methicillin-sensitive Staphylococcus aureus [MSSA]); 
• Certain drug-resistant bacteria: vancomycin-resistant Enterococci [VRE], methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-intermediate Staphylococcus aureus [VISA], vancomycin-resistant Staphylococcus aureus [VRSA]);
• Bacillus anthracis, Listeria monocytogenes (these are environmental bacteria).

Staphylococcus aureus, staining positive with Gram stain

Statins have also displayed antibacterial activity against a range of

Gram-negative bacteria. These include the following:

• Aggregatibacter, Actinomycetem comitans, Porphyromonas gingivalis (found in the mouth);
• Haemophilus influenzae, Moraxella catarrhalis (found in the nose and throat);
• Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis (found in the intestine);
• Acinetobacter baumannii, Pseudomonas aeruginosa, Salmonella typhimurium (environmental bacteria).

Scanning electron microscope image of E coli, which does not take up Gram stain

There is thus evidence of a very wide range of antibacterial effect of statins when tested in vitro. [Reference Ko HHT et al - see below]

The next stage would be in vivo testing, that is clinical trials. It is likely that in a trial the antibacterial statin would be given in addition to a conventional antibiotic, unless there is a major antibiotic resistance profile.

The anti-bacterial effect of statins

There is however clinical experience of the antibacterial effects of statins in humankind. Observations have been made of infections occurring in people taking statins and comparing these with people not taking statins. Some of these observations are as follows:

1. Survival from pneumonia was 83.1% in patients taking a statin compared to 75.5% in those not taking a statin.

2. In patients with previous myocardial infarction (MI), the risk of being admitted to hospital with pneumonia was 15% less in those taking a statin compared to those not taking a statin.

3. Wound healing and strength were much improved in patients taking statin compared to controls.

4. Taking a statin was associated with a 22% reduction in the risk of developing Clostridium difficile enteritis.

5. In a number of studies, taking a statin was associated with a greater than 50% benefit in the treatment of infections.

6. In patients treated in hospital for sepsis, the mortality rate was 15.7% in those taking atorvastatin. In those not taking a statin the mortality rate was almost double at 30.8% (survival 84.3% vs 69.2%)

Mortality rate in sepsis related to taking or not taking atorvastatin

References can be found below.

These studies are not controlled clinical trials but well structured observations that must not be disregarded.

The future use of statins in bacterial infections 

When administered in humans, all statins inhibit HMG-CoA reductase and thereby reduce cholesterol synthesis, but for reasons that are uncertain when tested in vitro statins exhibit a variation in antibacterial activity.

Of the various statins in use at present (for the purpose of reducing blood levels of cholesterol), simvastatin appears to have the best antibacterial effect, and atorvastatin is very similar. However this is still a quite weak effect compared to existing antibiotics to which an organism is sensitive. No doubt new statins will be developed to maximise antibiotic effect regardless of the effect on cholesterol synthesis. They are probably in the process of development now.

Even if statins on their own do not turn out to have adequate antibacterial actions, they could be used in conjunction with present antibiotics to improve action, and more importantly to reduce the emergence of resistant strains of bacteria. This a major opportunity for the future. It remains to be seen whether or not bacterial resistance to statins develops.

Significance in coronary heart disease

Treatment with statins gives a small benefit in the long-term prevention of death from coronary heart disease (CHD). The benefit seems to be greater and more immediate in someone who has just suffered from myocardial infarction (MI). This is a paradox: why should the benefit be immediate if the rationale of treatment is to reduce the blood level of cholesterol over  a long period of time?

If the benefit of statins were to be the result of cholesterol-lowering, the we would expect to see an arithmetic association – the greater the cholesterol-lowering, the greater the benefit (ie the lower the mortality rate).  This is what we are told happens, but it is not true. 

The data are almost entirely hidden from view and withheld  from public and even professional scrutiny. However, the embargo on the release of data occurred after the publication of the full data-set in the first primary prevention cholesterol trial, WOSCOPS, the West of Scotland primary prevention trial using pravastatin.

I have displayed in a previous Blog Post the cholesterol-lowering effect data from WOSCOPS, but I will display the figure again as it is so important.

In this figure, the first of the five groups (columns) showed no change in the blood level of cholesterol (0). It was assumed that this group represented the participants in the trial who did not take the statin (pravastatin) as prescribed. This group had the highest heart event rate (10.5 per 100 at 4.4 years) and it was the same as in the control group. 

The other four groups showed significant reductions in the blood levels of LDL-cholesterol (between 12 and 39%), indicating that the participants had taken the statin as directed. However there was no significant difference in the subsequent heart event and death rates (between 6 and 7.2%).

There is clearly a small benefit resulting from taking a statin, but there is no association between cholesterol-lowering and clinical benefit. This is an important anomaly, and it indicates that there must be a different mechanism whereby statins give clinical benefit.

It has been known for a long time that statins have an anti-inflammatory effect, and that CHD is an inflammatory disease of the coronary arteries. But now we can see a reason for the anti-inflammatory effect – statins are antibacterial. An antibacterial substance that is originally produced by another micro-organism is an antibiotic. Statins are thus originally antibiotics, but they are now synthesised rather than being produced in a biological broth.

I have indicated in previous Posts that the only plausible cause of CHD is an environmental biological agent, an infection. This also fits in with pandemic nature of CHD in the 20th century: only a biological agent could have such a profound effect in most continents simultaneously. The anti-bacterial property of statins is further but not conclusive evidence that CHD is due to one or more bacteria.

The immediate benefit from statin therapy following MI cannot be explained by the cholesterol-lowering property of statins, but it can certainly be explained by the antibacterial property.

Antibacterial statins can be taken by people at high risk of CHD, but the diet–cholesterol–hypothesis should be abandoned.

References and further details

The Lancet 20016 Vol 368, No 9529; 83–86. 
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)68971-X/abstract
Are statins analogues of vitamin D?
Grimes DS

Peer J. 2017 Oct 24;5:e3952. doi: 10.7717/peerj.3952. eCollection 2017.

Statins: antimicrobial resistance breakers or makers?

Ko HHT, Lareu RR, Dix BR, Hughes JD.

1. 
Clinical Medicine 2017 Vol 17, No 5: 403–7

Statin therapy in patients with community-acquired pneumonia

Frances S Grudzinska et al.

2,067 patient episodes of pneumonia were investigated retrospectively. Of these, 633 were taking a statin on admission and 1,434 were not. Simvastatin was the most commonly used statin (75.5%), followed by atorvastatin (19.4%), fluvastatin (4.7%) and rosuvastatin (0.2%).

The mean age of those on a statin was 76 years, and those not on a statin was 69 years. 355 (56.2) were men and 691 (48.2) were women.

Overall 1,609 (77.9) survived. The survival rate was 83.1% in those taking a statin and 75.5% in those not taking a statin.

2.
Cardiovascular Disorders 201616:24 https://doi.org/10.1186/s12872-016-0202-x

Statin use associated with a reduced risk of pneumonia requiring hospitalization in patients with myocardial infarction.

Chao-Feng Lin et al.

In 24,975 patients with previous myocardial infarction (MI), 2686 subsequently developed pneumonia severe enough to require admission to hospital. They were compared with 10,726 age- and sex-matched control patients. 

Statin use was associated with a 15 % reduced risk of pneumonia requiring hospital admission among the MI patients.

3. 
Ann Thorac Surg. 2014 Aug;98(2):756-64. doi: 10.1016/j.athoracsur.2014.02.089. 

Do statins have a role in the promotion of postoperative wound healing in cardiac surgical patients?

Fitzmaurice GJ et al.

Outcomes included a 30% earlier rate of wound healing,  80% greater wound-breaking strength, and faster wound healing rates (13.0 days vs 18.7 days).

4.
Gut. 2012 Nov; 61(11): 1538–1542.  doi:  10.1136/gutjnl-2011-301378

Statin use and the risk of Clostridium difficile

Christine Anne Motzkus-Feagans et al

Patients taking a statin medication were 0.78 times less likely to develop C difficile infection in the hospital than those who did not take a statin.

5. 
Arch Intern Med. 2009;169(18):1658-1667. doi:10.1001/archinternmed.2009.286

Statins for the Prevention and Treatment of Infections: a Systematic Review and Meta-analysis.

Tleyjeh IM et al.

This was a review os 16 study groups.

Nine studies investigated the role of statins in treating infections. The pooled adjusted effect estimate was 0.55 in favour of statins. 

Seven studies investigated infection prevention in sick patients. The pooled effect estimate was 0.57 in favour of statin use; there was some evidence of publication bias for this analysis.

6. 
Ann Intensive Care. 2015; 5: 9  doi:  10.1186/s13613-015-0049-9

Sepsis outcomes in patients receiving statins prior to hospitalization for sepsis.

Ouellette DR et al

Patients who received atorvastatin prior to hospital admission on account of sepsis and had statins continued in hospital had a very low mortality rate (15.7%) that was significantly less than that of those patients who never received statins (30.8%).

7.
10.1161/CIRCULATIONAHA.117.027966 
Antonio J. Vallejo-Vaz et al. 

LDL-Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men with Primary Elevations of LDL-Cholesterol Levels of 190 mg/dL or Above: Analyses from the WOSCOPS 5-year Randomised Trial and 20-year Observational Follow-Up.